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Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Multiple tumor suppressor pathways negatively regulate telomerase
Shiaw Yih Lin1, Stephen J Elledge
1Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Cell
|July 3, 2003
Summary
Telomerase (hTERT) is repressed in most cells but active in cancer. This study identified three tumor suppressor pathways (Mad1/c-Myc, SIP1, and Menin) that regulate hTERT, revealing insights into cancer development.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Telomerase expression is typically repressed in somatic cells but active in stem cells and many human cancers.
- Telomerase activity is hypothesized to be crucial for tumorigenesis and maintaining stem cell properties.
- Understanding telomerase regulation is key to developing cancer therapies.
Purpose of the Study:
- To identify negative regulators of human telomerase reverse transcriptase (hTERT) expression.
- To elucidate the role of tumor suppressor and oncogene pathways in controlling telomerase activity.
Main Methods:
- Utilized a general genetic screen to identify negative regulators of hTERT.
- Investigated the Mad1/c-Myc, TGF-beta/SIP1, and Menin pathways in relation to hTERT repression.
- Assessed the impact of Menin depletion on primary human fibroblasts and transformation phenotypes.
Main Results:
- Identified three distinct tumor suppressor/oncogene pathways involved in hTERT repression: Mad1/c-Myc, SIP1 (a TGF-beta target), and Menin.
- Confirmed the Mad1/c-Myc pathway's role in hTERT regulation.
- Demonstrated that SIP1 mediates TGF-beta-regulated hTERT repression.
- Showed Menin directly represses hTERT and its depletion immortalizes fibroblasts and promotes transformation.
Conclusions:
- Multiple tumor suppressor and oncogene pathways coordinate to repress hTERT expression.
- Telomerase reactivation in human tumors likely occurs through oncogenic mutations that disrupt these regulatory pathways.
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